Glasgow Royal Infirmary

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Objective Risankizumab is an interleukin-23 p19 subunit inhibitor which received approval for Crohn’s disease (CD) by UK licensing authorities in May 2023. Our aim was to evaluate the real-world outcomes of risankizumab in the UK. Design We conducted a retrospective, multicentre, cohort study of patients with CD treated with risankizumab across 25 health boards in the UK between 1 January 2021 and 1 November 2024. Our primary outcome was treatment persistence at 6 months. Our secondary endpoints were steroid-free clinical remission (Harvey-Bradshaw index <5), C-reactive protein (CRP) remission (CRP ≤5 mg) and faecal calprotectin (FCAL) remission (FCAL <250 µg/g). Results We included 763 patients with a median follow-up time of 27 weeks (IQR 18–41 weeks) with a total of 432 and 110 patients having 6-month and 12-month data available. The median number of advanced therapy exposures was 3 (2–4), with 92% (704/763) having failed anti-tumour necrosis factor therapy and 72% (548/763) having failed ustekinumab. Treatment persistence at 6 and 12 months was 95.4% and 89.2%, respectively. Unadjusted persistence rates for ustekinumab-naive versus ustekinumab-exposed patients were 92.7% vs 95.3% and 89.0% vs 74.2% at 6 and 12 months, respectively (p=0.62). Rates of clinical, CRP and FCAL remission were 52% (123/236), 53% (169/319) and 44% (69/156) at 6 months. Rates of clinical remission for ustekinumab naive versus exposed were 57% (29/51) vs 51% (94/185) (p=0.54) 6 months. Adverse events occurred in 17% (n=127) of the cohort, of which 12% (n=92) were serious. Conclusion Risankizumab was effective in a large, real-world, medically refractory CD cohort with excellent persistence and good clinical and biochemical remission rates.

Abstract Background Excess fat mass and myopenia have been associated with adverse disease outcomes in Crohn’s disease (CD). Despite increasing use of advanced therapies in CD, tools that predict treatment response are lacking. We explored if body composition could predict response to standard-dose adalimumab in active CD. Methods This was a secondary analysis of BIOPIC study, a multicentre randomised controlled trial investigating the effect of partial enteral nutrition in patients with active CD commencing adalimumab therapy. Anthropometry and body composition (bioelectrical impedance analysis, Tanita DC-360P) was measured. Fat mass and fat-free mass were standardised for height (body fat index-BFI and fat-free mass index-FFMI). Patient follow-up was undertaken at 6 and 12 weeks to assess response to adalimumab. Clinical response or remission was assessed by Harvey-Bradshaw Index (HBI) and defined as reduction in HBI ≥ 3 or HBI < 5. Biochemical response (CRP <10) and faecal calprotectin (FCAL) normalisation (<200) were assessed. Therapeutic adalimumab drug levels and anti-drug antibodies (ADAs) were measured. Treatment outcomes and body composition parameters were analysed using logistic regression. Results Seventy-eight participants were included (mean age 40.8 [SD 14.5], 41 (53%) female). Baseline BFI (OR 1.24, CI 1.09-1.41, p = 0.001) and fat mass (OR 1.12, CI 1.05-0.19, p = <0.001) were significant predictors of failure to achieve response or remission to adalimumab by week 12 using a univariate logistic regression model; FFMI was not (OR 1.20, CI 0.98-1.46, p = 0.082). There was no correlation between body composition and baseline disease severity indices or biomarkers. Fat mass and BFI remained predictors of failure to achieve response or remission (OR 1.16, CI 1.07-1.26, p = 0.001, OR 1.27, CI 1.03-1.47, p = 0.002 respectively) after adjusting for disease duration, disease severity (HBI), sex and corticosteroid use. Fat mass also predicted failure to normalise CRP (OR 1.07, CI 1.01 – 1.13, p = 0.025) but body composition parameters could not predict normalisation of FCAL. Sixty-six participants had adalimumab drug levels and ADAs measured. Fat mass (%) was negatively correlated with adalimumab drug levels (r = -0.409, p < 0.001), positively correlated with ADAs (r = 0.300, p = 0.014) and predicted formation of ADAs to adalimumab (OR 1.07, CI 1.00-1.15, p = 0.043). Conclusion Adiposity predicts risk of treatment failure with standard dose adalimumab. This may be related to suboptimal therapeutic drug levels and increased risk of immunogenicity. Intensive monitoring of therapeutic drug levels and adjustment of adalimumab dose according to adiposity may be considered. Conflict of interest: Dr. Fattah, Sharif: No conflict of interest White, Bernadette: No conflict of interest Campbell, Iona: No conflict of interest Fandinga, Catarina: No conflict of interest Clowe, Jennifer: No conflict of interest Brownson, Emily: No conflict of interest Ho, Gwo-Tzer: No conflict of interest Robertson, Elaine: No conflict of interest Mowat, Craig: No conflict of interest Gaya, Daniel: No conflict of interest Kefayat, Amirhosein: No conflict of interest Din, Shahida: No conflict of interest Seenan, John Paul: No conflict of interest Macdonald, Jonathan: No conflict of interest Gerasimidis, Konstantinos: Grant: Nestle Health Science, Nutricia-Danone, Mylan Personal Fees: Abbott, Baxter, Nestle Health Science, Nutricia-Danone, Servier, Janssen

Abstract Background Microbiome modifying treatments show potential in favourably influencing outcomes of patients with mild-moderate Ulcerative Colitis (UC). In a proof-of-concept study, we tested the gastrointestinal tolerability of a novel, “eubiotic” diet (UC-TREAT), and assessed its effects on the gut microbiome and short chain fatty acid (SCFA) production in individuals with UC and healthy controls (HC). Methods In a controlled prospective trial, 36 adults (18 HC and 18 with quiescent UC, defined as SCCAI ≤5) underwent a 10-day “run-in” phase, followed by a 5-day introductory “ramping” phase, and a 10-day “full” dietary intervention with UC-TREAT. UC-TREAT is rich in fermentable carbohydrates (providing 35g/day fibre in addition to habitual intake), and includes daily consumption of 5 different fermented foods, 2 types of berries, and a multivitamin supplement. Faecal samples were collected before and after each study phase, in which microbiome (16S rRNA), bacterial load (quantitative PCR), SCFA (GC-FID) and faecal calprotectin (FCAL) were assessed. Gastrointestinal tolerance (GSRS-IBS), disease activity (SCCAI) and dietary intake were assessed throughout the study. Results Fibre intake doubled during UC-TREAT (9.8 vs 20.8g/1000kcal/day, p < 0.001) and fermented food consumption increased by 4.3 portions/d (p < 0.001) in all participants. In both participant groups, an increase was observed in faecal acetate [median (Q1:Q3) µmol/g: UC: +11.1 (-3.73, 21.5); HC: +15.2 (-0.57, 36.6), both p < 0.01], total SCFA [UC: +11.6 (2.38, 22.1) µmol/g, p = 0.006; HC: +23.1 (-0.76, 53.2), p = 0.015], and bacterial load [log10 16S rRNA gene copies/g, UC: +0.07 (0, 0.22), p = 0.03; HC: +0.06 (-0.04, 0.14), p = 0.07]. Butyrate also increased in UC participants [+2.79 (-0.75, 4.88) µmol/g, p = 0.03). UC participants reported a short-term increase in bloating [median score: +2 (0, 4.3), p = 0.012], while HC reported prolonged bloating [+2.5 (1, 3), p = 0.001] and a transient rise in constipation [+1 (0, 3), p = 0.03] and satiety [0 (0, 1), p = 0.03]. Disease activity score increased [0 (0, 1), p = 0.012], while all UC participants remained in clinical remission and FCAL remained unchanged in UC, but decreased in HC [-3.15 (-10.3, 0.71) mg/kg, p = 0.02]. Microbiome composition changed in UC patients (R2=1.2% p < 0.01), but not in HC; Abundance of Streptococcus, and Anaerostipes hadrus, a butyrate producer, increased in UC (p < 0.001). Conclusion UC-TREAT increased fibre-originating faecal SCFA, bacterial load, and SCFA-producing taxa, without negatively affecting FCAL or GI tolerance in quiescent UC. These proof-of-concept results should be replicated in a larger, well-controlled RCT. Conflict of interest: Ms. Mckirdy, Shona: No conflict of interest Gaya, Daniel: No conflict of interest Russell, Richard K.: Grant: Nestec Other: Abbvie, Celltrion, Janssen, Lilly, Nestle, Pharmacosmos, Pfizer Hansen, Richard: Personal Fees: Dr Hansen has received consultancy fees and travel support from 4D pharma. Macdonald, Jonathan: No conflict of interest Seenan, John Paul: No conflict of interest Nichols, Ben: No conflict of interest Koutsos, Athanasios: No conflict of interest Gerasimidis, Konstantinos: Grant: Nestle Health Science, Nutricia-Danone, Mylan Personal Fees: Abbott, Baxter, Nestle Health Science, Nutricia-Danone, Servier, Janssen

Introduction: Although internal fixation surgery of displaced ankle fractures is amongst the most commonly performed operations, there is little published on long-term outcomes. The true incidence of posttraumatic osteoarthritis (PTOA) requiring further intervention is not well known. This study aims to establish the incidence of complications and long-term outcomes, specifically the development of arthritis. Furthermore, it aims to determine the effect of patient characteristics on these outcomes. Method: All patients who underwent ankle fixation at Glasgow Royal Infirmary between January 2009 and December 2010 were retrospectively identified through our departmental database. Patient demographics, comorbidities and complications including infection, non-union, further surgery, and development of PTOA were recorded. Two proportion hypothesis testing was used to establish whether patient characteristics affected outcomes. Results: 330 patients underwent ankle fixation surgery during the study period. There was a 1.2% and 1.5% incidence of superficial and deep infection respectively. Revision fixation surgery was necessary in 5/330 patients (1.5%), however 21.5% underwent further surgery including removal of metalwork. The latest clinical information showed 3.6% (12/330) developed PTOA and only 5 required surgeries including 3 ankle fusions. There was a statistically significant increase in the rate of delayed unions (P=0.041) in smokers. There was also a higher rate of deep infection, delayed union and revision surgery in diabetic patients and a higher rate of PTOA and requirement for surgical management of PTOA in overweight patients, although these did not reach statistical significance. Conclusion: Our results show that internal fixation surgery for ankle fractures is associated with low incidences of both short-term complications and development of arthritis in the long-term. In our study, smokers had higher rates of delayed union but there was no significant correlation between patient characteristics and comorbidities on other outcomes.

Long COVID presents an unmet therapeutic need. To determine the effects of a resistance exercise intervention on exercise capacity, health status, and safety among adults after COVID-19 infection. A 2-arm, multicenter, randomized clinical trial including 233 adults with a hospital or community diagnosis of COVID-19 infection in the preceding 12 months was undertaken from June 1, 2021, to April 26, 2024. The intervention group comprised 117 individuals, and the control group comprised 116 individuals. A total of 224 individuals at baseline and 193 individuals at 3 months completed Incremental Shuttle Walk Tests. The intervention group received the personalized resistance exercise intervention for 3 months, and the control group received treatment as usual. The primary outcome was the distance achieved (in meters) in the Incremental Shuttle Walk Test undertaken 3 months after randomization. Secondary outcome measures included health-related quality of life (measured by the European Quality of Life 5-Dimension 5-Level Instrument [EQ-5D-5L]), anxiety and depression (measured by the Patient Health Questionnaire), and grip strength. A total of 233 adults (median age, 53.6 years [IQR, 43.8-60.8 years]; 146 women [62.7%]; 91 [39.1%] hospitalized with COVID-19 infection) were randomized (117 [50.2%] to the intervention group and 116 [49.8%] to the control group). The median percentage adherence with the exercise intervention was 71.0% (IQR, 47.8%-96.8%), equivalent to performing the exercises 5 days per week. The mean (SD) distance achieved in the Incremental Shuttle Walk Test was 328 (225) m for 224 individuals at baseline and 389 (249) m for 193 individuals at follow-up. The mean (SD) change in Incremental Shuttle Walk Test distance at 3 months compared with baseline was 83 (118) m in the intervention group (n = 94) and 47 (95) m in the control group (n = 98) (adjusted mean difference, 36.5 m [95% CI, 6.6-66.3 m]; P = .02). By 3 months, compared with the control group, greater improvements in the intervention group were also observed for the health-related quality of life utility score (EQ-5D-5L) (0.06 [95% CI, 0.01-0.11]; P = .02), Patient Health Questionnaire category (0.5 [95% CI, 0.2-0.8]; P = .01), and handgrip strength (2.6 kg [95% CI, 0.9-4.2 kg]; P = .002). In this randomized clinical trial, a 3-month program of resistance exercise among adults after COVID-19 infection appeared to improve walking distance, health-related quality of life, anxiety, depression, and grip strength. This pragmatic intervention may be a generalizable therapy for individuals with persisting physical symptoms after COVID-19 infection. ClinicalTrials.gov Identifier: NCT04900961.

<h3>Background</h3> Clinical outcomes for NTM-PD are often poor. The NTM Network UK Standards of Care were launched in 2024 to support consistent, high-quality practice including pharmacological and non-pharmacological treatment. We aimed to document NTM-PD management prior to this to identify opportunities to improve care. <h3>Methods</h3> Centres were invited via the NTM Network UK to complete an online retrospective survey. At each site, anonymised clinical data were recorded from three consecutive adults (≥18) newly diagnosed with NTM-PD from 1 January 2022. <h3>Results</h3> 48 centres participated (Northern England, n=12; Southern England, n=12; London, n=9; Wales, n=7; Midlands, n=6; Scotland, n=2) They reported having the following resources: physiotherapy for airway clearance (n=42/48, 88%), dietitian and pulmonary rehabilitation (each n=32, 67%), specialist nurse (n=30, 63%), and health psychology (n=9, 19%). Respondents contributed data on 137 patients. 72 (53%) were female and 115 (84%) identified as White-British. 45 (34%) were aged 61–70. 62 (45%) had COPD and 55 (40%) bronchiectasis. Common radiological findings were nodular-bronchiectatic change (n=62, 45%), fibro-cavitary disease (n=40, 29%), and emphysema (n=39, 28%). <i>Mycobacterium avium complex</i> (MAC) was identified in 106 (77%), <i>M. kansasii</i>(n=14, 10%) and <i>M. abscessus</i> (n=9, 7%). Eighty-one (59%) patients were discussed in an MDT. Treatment plans included involvement of specialist nurses (n=91, 66%), physiotherapists (n=52, 38%), dietitians (n=34, 25%), and pulmonary rehabilitation (n=16, 12%). Forty-two (31%) were advised on airway clearance using Active Cycle Breathing, 25 (18%) Positive Expiratory Pressure devices, 17 (12%) mucoactive drugs, and 12 (9%) hypertonic saline. Written resources were provided to 39 (28%) patients, 22 (16%) were directed to patient-focused websites, and 13 (10%) signposted to peer-support networks. During a median follow-up from diagnosis of 21 (IQR 14–29) months, 124 (91%) started antibiotics for NTM-PD. Forty-five (33%) remain on follow-up and using antibiotics, 53 (39%) are not on antibiotics, 26 (19%) were discharged, and 12 (9%) died. <h3>Conclusion</h3> This UK-wide assessment of NTM-PD management reveals significant variation in available services and care provided. Most patients started specific antimicrobials, though non-medical health care support and patient information provision were limited. We have identified important areas for re-audit against the 2024 Standards.

For decades, most critical care patients have survived hospitalisation, supporting increased attention on the long-term critical illness recovery. The term 'Post-Intensive Care Syndrome' was coined in 2012 to raise awareness of long-term impairment in physical, cognitive and/or mental health after critical illness. However, the incidence of these impairments has persisted over the past decade, reaching as high as 60% and remains a major public health problem.Aiming to set a research agenda to address evidence gaps in critical illness recovery over the next 10 years, we invited key international opinion leaders from diverse clinical and methodological backgrounds to a roundtable meeting in June 2024 to assess the progress of post-critical illness recovery research and outline a future research agenda to address the unmet needs of critical illness survivors over the next decade.An early outcome from the meeting was to conduct a thematic analysis of critical care recovery literature, which highlighted the need for effective expectation management, ongoing patient support and education throughout recovery, integration between inpatient and community care, caregiver support and opportunities to reconnect with the intensive care unit.Participants identified conceptual challenges concerning current terminology and scope, population heterogeneity and phenotyping, and outcome definitions. Methodological challenges were identified around study design, with a call to shift to contemporary trial designs, incorporating qualitative methods. Translation into clinical practice will require interdisciplinary engagement.The roundtable concluded that a roadmap should be developed to guide clinical and research efforts over the coming decade, with the aim of developing a precision recovery approach.

The aim of radioactive iodine (RAI) in differentiated thyroid cancer (DTC) is ablation of thyroid remnant and/or treatment of residual disease. This review compares guidelines recommending the use of RAI (or not) in DTC, with a focus on randomized trials in low-risk DTC. Molecular genotyping offers therapeutic options in advanced RAI-refractory DTC. The ESTIMABL2 and IoN trials suggest that thyroidectomy (with or without central compartment lymph node dissection) followed by surveillance is sufficient in low-risk DTC, despite key differences in inclusion criteria, recurrence-definition, and monitoring protocols. RAI practice is tailored in many aspects: selection of intermediate-risk DTC for RAI and activity based on individual factors, including early dynamic risk assessment; lesional dosimetry in advanced DTC; restrictions following RAI; and choice of systemic therapy in the RAI-refractory setting. RAI in DTC is evolving towards a risk-adapted model. Escalating evidence indicates that RAI may be safely withheld in a large proportion of low-risk DTC. Optimal management of intermediate-risk DTC remains controversial, due to heterogeneity in clinical and pathological characteristics and conflicting data over survival advantage. Well designed studies incorporating molecular genotype may be key in identifying those most likely to benefit from RAI and in elucidating mechanisms of RAI-resistance.